Package leaflet: Information for the patient

CORTRIUM 20 mg/2 ml powder and solvent for injectable solution, 40 mg/2 ml powder and solvent for injectable solution, 120 mg/2 ml powder and solvent for injectable solution, 500 mg powder for injectable solution

Methylprednisolone sodium succinate
Generic medicine
Please read all of this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or the doctor treating the child or the pharmacist.
This medicine has been prescribed for you and/or for the child only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
If you and/or the child experience any adverse reactions, including those not listed in this leaflet, contact your doctor or the doctor treating the child or the pharmacist. See section 4.

Contents of this leaflet

What CORTRIUM is and what it is used for
What you need to know before using CORTRIUM
How to use CORTRIUM
Possible side effects
How to store CORTRIUM
Contents of the pack and other information

1. What CORTRIUM is and what it is used for

CORTRIUM contains the active substance methylprednisolone sodium succinate. Methylprednisolone sodium succinate
belongs to a group of medicines called corticosteroids. Corticosteroids are substances naturally produced
by the body and are important for many bodily functions.
CORTRIUM is used in adults and children over three years of age for the treatment of:

diseases in which the body is unable to produce sufficient amounts of natural corticosteroids, for example due to adrenal gland problems such as adrenal insufficiency;
skin diseases (pemphigus, severe erythema multiforme, exfoliative dermatitis);
allergic diseases (bronchial asthma, contact dermatitis, serum sickness, drug allergies, angioneurotic edema, urticaria, anaphylactic shock);
intestinal diseases (ulcerative colitis, segmental ileitis);
blood cancers (e.g. leukaemia in adults and children);
brain diseases (e.g. conditions caused by a tumour or trauma);
lung diseases in patients with AIDS;
cancers affecting the lymphatic glands (lymphomas in adults);
conditions characterized by fluid accumulation (edematous states); very advanced-stage cancers (palliative therapy). CORTRIUM may also be used for relapses of symptoms in multiple sclerosis and systemic lupus erythematosus, or for other stressful conditions.

CORTRIUM may also be used for the following conditions:

generalized skin disease (neurodermatitis);
acute rheumatic fever ( acute inflammatory disease affecting the joints, heart, skin, and central nervous system);
oesophageal burns;
prevention of nausea and vomiting associated with chemotherapy for cancer treatment;
severe Pneumocystis jiroveci lung infections in patients with A.I.D.S. (adjunctive therapy).

Please consult your doctor if you are unsure why this medicine has been prescribed for you or your child.

2. What you need to know before using CORTRIUM

Do not use CORTRIUM if you and/or the child:

are allergic to sodium methylprednisolone succinate or to any of the other ingredients of this medicine (listed in section 6);
have a fungal infection that has spread to several organs or throughout the body;
the child was born prematurely, is a newborn, or is under three years of age.

CORTRIUM will not be administered to you/to the child via injections into the back (intrathecal/epidural administration).
You and/or the child must not be vaccinated with "live" or "live attenuated" vaccines during treatment with CORTRIUM.
Warnings and precautions
Talk to your doctor or pharmacist BEFORE using this medicine if:

you need to undergo skin sensitivity tests;
you have or have previously had tuberculosis;
you are under particular conditions of stress. In such cases, your doctor will prescribe a higher dose of this medicine for you or your child;
you have Cushing's syndrome, a disease characterized by excessive production of natural corticosteroids in the body. CORTRIUM may worsen your or your child’s condition;
your thyroid gland is underactive ( hypothyroidism ). In this case, doses of CORTRIUM should be reduced;
you have diabetes;
you suffer from epileptic seizures;
you suffer from myasthenia gravis, a disease causing muscle weakness and fatigue, or you are scheduled for surgery with general anesthesia involving the use of muscle-blocking drugs (e.g. pancuronium). In this case, there is an increased risk that CORTRIUM may cause muscle-related problems;
you have an eye infection caused by the Herpes simplex virus;
you suffer from high blood pressure ( hypertension);
you have elevated levels of fats in the blood ( dyslipidemia);
you have heart problems ( heart failure);
you suffer from or are predisposed to developing blood clots in the veins;
you have a stomach ulcer or other serious stomach or intestinal problems (see "How to use CORTRIUM");
you have kidney problems;
you have scleroderma (also known as systemic sclerosis, an autoimmune disease), as the use of corticosteroids may increase the risk of a serious complication called scleroderma renal crisis;
you have a brain injury caused by trauma;
you have liver cirrhosis, a liver disease;
you are being treated with non-steroidal anti-inflammatory drugs (e.g. acetylsalicylic acid) (see section "Other medicines and CORTRIUM") and have reduced prothrombin activity, a protein that helps blood to clot;
you have a type of tumor called pheochromocytoma;
you suffer from peritonitis or other gastrointestinal disorders, as glucocorticoid therapy may mask symptoms such as perforation, obstruction, or pancreatitis.
If your thyroid is overactive (hyperthyroidism). If, during treatment with methylprednisolone, you experience muscle weakness, muscle pain, cramps, or stiffness, contact your doctor immediately. These may be symptoms of a condition called thyrotoxic periodic paralysis, which may occur in patients with overactive thyroid (hyperthyroidism) treated with methylprednisolone. Additional treatment may be required to relieve this condition.

If you have cancer, you are at high risk of developing tumor lysis syndrome, which may occur when corticosteroids are used during cancer treatment. Inform your doctor if you have cancer and experience symptoms of tumor lysis syndrome such as muscle cramps, muscle weakness, confusion, irregular heartbeat, vision loss or visual disturbances, and shortness of breath.
Inform your doctor or the doctor treating your child if any of the following conditions appear or worsen DURING treatment with this medicine (see also section 4 “Possible side effects”):

Infections. This medicine may reduce resistance to various infections, mask certain infection symptoms, worsen existing infections, or cause reactivation or worsening of hidden old infections. New infections may also occur during treatment with Cortrium. Therefore, certain infections may occur more easily during treatment, for example, chickenpox and measles. These infections may be mild, severe, and sometimes fatal. Your doctor will closely monitor you for the development of infections and may consider, if necessary, interrupting treatment or reducing the dose.
Kaposi's sarcoma, a skin tumor. In this case, discontinue treatment with CORTRIUM;
Severe allergic reactions;
onset or worsening of mental disorders (e.g. depression). Inform people living with you about the possible effects of this medicine;
Fat accumulation compressing the spinal cord;
Eye problems;
changes in heart rhythm ( cardiac arrhythmias ), reduced heart rate ( bradycardia ), circulatory collapse, and cardiac arrest;
severe inflammation of the pancreas or liver;
hepatobiliary disorders (reversible after discontinuation);
Osteoporosis (fragile bones);
Swelling in various parts of the body, especially in the legs and ankles, or changes in normal blood mineral levels;
blurred vision or other visual disturbances.

You or your child must not be vaccinated with "live" or "live attenuated" vaccines during treatment with CORTRIUM (see section “Do not use CORTRIUM if you and/or the child”). However, you may receive inactivated or killed vaccines, although their effectiveness may be reduced.
Oral anticoagulants (medicines taken by mouth to prevent blood clotting) may increase the risk of bleeding when taken together with Cortrium. In some cases, the effectiveness of oral anticoagulants may be reduced. Your doctor may need to frequently monitor your bleeding risk by performing additional blood tests during treatment with Cortrium. The dose of Cortrium may also need to be adjusted if necessary.
For athletes
Using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.
Children
This medicine must not be given to premature infants, newborns, or children under three years of age.
Long-term or high-dose treatment with CORTRIUM may cause growth retardation, increased intracranial pressure, and pancreatitis in children.
The use of methylprednisolone in premature newborns may lead to the development of hypertrophic cardiomyopathy (thickening of the heart walls).
Elderly
If you are elderly, long-term treatment with CORTRIUM may increase the risk of developing osteoporosis, excessive fluid retention in the body, and increased blood pressure. Your doctor will evaluate your condition and administer this medicine cautiously.
Other medicines and CORTRIUM
Inform your doctor or pharmacist if you and/or the child are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
Some medicines may increase the effects of CORTRIUM, and your doctor may need to monitor you closely if you are taking these medicines.
The following medicines may affect the activity of CORTRIUM or CORTRIUM may affect the efficacy and/or toxicity of the following medicines:

isoniazid, troleandomycin, clarithromycin, and erythromycin (antibiotics);
methotrexate, used for the treatment of tumors and autoimmune diseases;
rifampicin (antibiotic for tuberculosis);
phenobarbital, phenytoin, and carbamazepine (medicines for seizures);
aprepitant and fosaprepitant (medicines for nausea and vomiting);
itraconazole, ketoconazole, and amphotericin B (medicines for fungal infections);
HIV medicines such as indinavir, ritonavir, and cobicistat (medicines against HIV virus);
aminoglutethimide (medicine for excessive production of natural corticosteroids);
diltiazem (medicine used for heart problems or high blood pressure);
ethinylestradiol/norethisterone (hormones used in combination as oral contraceptives);
cyclosporine, cyclophosphamide, and tacrolimus, medicines for preventing organ transplant rejection and for autoimmune diseases;
oral anticoagulants, medicines taken by mouth to prevent blood clotting;
neuromuscular blockers such as pancuronium and vecuronium (medicines causing muscle relaxation);
anticholinesterases such as pyridostigmine and neostigmine (medicines for muscle diseases like myasthenia gravis and Alzheimer's disease);
antidiabetics (medicines for diabetes);
aspirin (acetylsalicylic acid);
diuretics (medicines that increase urine production);
xanthines (e.g. theophylline) and beta-2 agonists (e.g. salbutamol), medicines for asthma;
antihypertensives, medicines used to lower blood pressure;
digoxin, used for the treatment of heart failure and/or irregular heartbeat;
psychotropic medicines (anxiolytics and antipsychotics), medicines used to treat anxiety and mental disorders.

CORTRIUM and beverages
You and/or the child must not drink grapefruit juice during treatment with CORTRIUM, as the efficacy and toxicity of this medicine may increase.
Pregnancy, breastfeeding, and fertility
If you are pregnant, think you might be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before using/receiving this medicine.
Pregnancy
If you use this medicine during pregnancy, especially at high doses and for prolonged periods, the baby may experience adverse effects at birth. Therefore, your doctor will prescribe CORTRIUM only if strictly necessary.
Breastfeeding
CORTRIUM passes into breast milk and may cause adverse effects in the baby. If you are breastfeeding, your doctor will prescribe CORTRIUM only if strictly necessary.
Fertility
Based on currently available information, this medicine may reduce fertility.
Driving and using machines
Do not drive or operate machinery if during treatment with CORTRIUM you experience dizziness, vertigo, visual disturbances, fatigue, euphoria, or mood disturbances.
CORTRIUM contains sodium
CORTRIUM 20 mg/2 ml, 40 mg/2 ml, 120 mg/2 ml: contains less than 1 mmol (23 mg) of sodium per vial, i.e., it is practically "sodium-free".

3. How to use CORTRIUM

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

Your doctor will determine the dose of CORTRIUM based on the severity of the condition being treated and your health status (either yours or your child's). During treatment, your response to the medication will be monitored, and therefore the dose may be adjusted. Your doctor will explain how to taper the dose before stopping CORTRIUM.

Adults
The recommended initial dose is 10 mg to 40 mg, administered intravenously (into a vein) over several minutes.
Subsequent doses may be given either intravenously or intramuscularly (into a muscle).
CORTRIUM may be administered at high doses for up to a maximum of 48–72 hours.
In such cases, the recommended dose is 30 mg/kg body weight administered intravenously over a 30-minute period. This dose may be repeated every 4–6 hours within 48 hours.

Children over 3 years of age
The doctor will determine the dose based on the severity of the child's condition, response to therapy, age, and body weight.
The recommended dose should not be less than 0.5 mg/kg body weight per day.

Method of administration
CORTRIUM is administered intravenously (by injection into a vein), intramuscularly (into a muscle), by intravenous infusion (into a vein), or via an infusion pump (intravenous infusion using an electronic device).
In an emergency, the intravenous route is preferred.
Intravenous administration must be performed by trained healthcare personnel.

If you use/administer more CORTRIUM than you should
If a dose of this medicine significantly higher than prescribed is used, acute toxicity and even death may occur, although rarely.
Seek immediate medical attention or go to the nearest hospital if you and/or your child have accidentally taken an excessive dose of CORTRIUM.

If you forget to use CORTRIUM
Do not take a double dose to make up for the missed dose.
If you realize you have missed a dose, consult your doctor.

If you stop using CORTRIUM
You or your child must not stop taking CORTRIUM suddenly. CORTRIUM may cause reduced function of the adrenal glands, which produce natural corticosteroids, and abrupt discontinuation may lead to death.
Additionally, sudden interruption of CORTRIUM treatment may lead to withdrawal symptoms such as: anorexia, nausea, vomiting, excessive drowsiness, headache, fever, muscle and joint pain, skin desquamation, weight loss, low blood pressure, and psychiatric disturbances.
When stopping treatment, doses must be gradually tapered. Your doctor will advise you on the correct method to do this (see "How to use CORTRIUM").

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor if you experience any of the following side effects:

Frequency not known (frequency cannot be estimated from the available data):

infections, including infections occurring when the body's immune defences are very low
increased number of white blood cells in the blood
hypersensitivity to the medicine
severe allergic reaction, for example swelling of the face, tongue and throat with difficulty swallowing and breathing (angioedema)
urticaria
rounded or moon-shaped face (Cushingoid appearance)
reduced secretion of hormones from the pituitary gland (a gland located at the base of the brain)
withdrawal syndrome (see section 3 “If you stop treatment with CORTRIUM”)
metabolic acidosis
glucose metabolism disorder and worsening of pre-existing diabetes
increased loss or retention of acidic substances from the body
high levels of fats in the blood
fluid and sodium retention in the body
increased levels of urea in the blood
increased appetite and body weight
accumulation of fatty tissue in specific body areas
increased body fat
psychiatric disorders such as: depression, euphoria, manic behaviour, delirium, hallucinations, schizophrenia, altered perception of reality and thought disorders, emotional disturbances (e.g. mood swings, emotional dependence, suicidal ideation), personality changes, confusion, anxiety, abnormal behaviour, insomnia, irritability
increased pressure of the fluid within the skull
seizures
memory difficulties
thought disorders affecting awareness of reality
dizziness
headache
fat accumulation compressing the spinal cord
cataract
increased internal eye pressure
protruding eyes
reduced vision in the central visual field
retinal and choroidal membrane disease
heart problems (heart failure) in susceptible patients
irregular heartbeat
formation of blood clots in veins and lungs
increased blood coagulation
increase or decrease in blood pressure
warmth and skin redness (flushing)
hiccups
stomach and intestinal ulcers with possible bleeding and perforation
inflammation of the pancreas
abdominal inflammation (peritonitis)
inflammation of the oesophagus with or without ulcers
abdominal distension and pain
difficulty digesting
nausea, vomiting and diarrhoea
inflammation of the liver
delayed wound healing
thinning and fragility of the skin
discoloured skin patches
atrophy of the skin and its appendages (hair, nails)
pus formation
swelling
bruising
appearance of small red spots or thin purplish streaks on the skin
increased hair growth
skin redness, rashes
itching
acne
excessive sweating
bone fragility (osteoporosis), bone tissue death and loss
muscle and joint pain, muscle disorders, reduced muscle mass
muscle weakness
joint rupture (especially in the foot) causing pain and/or swelling
irregular menstruation
reaction at the injection site
fatigue, malaise
abnormal laboratory tests assessing liver function
possible liver damage, hepatitis, increased liver enzymes
decreased potassium levels in the blood
increased calcium levels in the urine
reduced response to skin tests
vertebral fractures (from trauma or spontaneous), tendon rupture, particularly of the Achilles tendon
blurred vision

Additional side effects in children
Frequency not known (frequency cannot be estimated from the available data):

growth retardation

Reporting of side effects
If you or your child experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store CORTRIUM

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp.".
The expiry date refers to the last day of that month. The stated expiry date applies to the product in its original packaging, stored correctly.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
CORTRIUM 20 mg/2 ml powder and solvent for injectable solution
CORTRIUM 40 mg/2 ml powder and solvent for injectable solution
CORTRIUM 120 mg/2 ml powder and solvent for injectable solution
CORTRIUM 500 mg powder for injectable solution
Store this medicine below 25°C.
Period of validity after reconstitution: use within 4 hours.

6. Package Contents and Other Information

What CORTRIUM Contains
The active substance is methylprednisolone (as methylprednisolone sodium succinate).
CORTRIUM 20 mg/2 ml powder and solvent for injectable solution
Each vial of powder contains 20 mg of methylprednisolone (equivalent to 663.0 mg of methylprednisolone
sodium succinate).
The other component is: water for injectable preparations.
CORTRIUM 40 mg/2 ml powder and solvent for injectable solution
Each vial of powder contains 40 mg of methylprednisolone (equivalent to 53.0 mg of methylprednisolone
sodium succinate).
The other component is: water for injectable preparations.
CORTRIUM 120 mg/2 ml powder and solvent for injectable solution
Each vial of powder contains 120 mg of methylprednisolone (equivalent to 159.0 mg of methylprednisolone
sodium succinate).
The other component is: water for injectable preparations.
CORTRIUM 500 mg powder for injectable solution
Each vial of powder contains 500 mg of methylprednisolone (equivalent to 663.0 mg of methylprednisolone
sodium succinate).

Description of the Appearance of CORTRIUM and Package Contents
CORTRIUM 20 mg/2 ml powder and solvent for injectable solution is available in packages containing 1 vial with powder + 1 ampoule of solvent (2 ml).
CORTRIUM 40 mg/2 ml powder and solvent for injectable solution is available in packages containing 1 vial with powder + 1 ampoule of solvent (2 ml).
CORTRIUM 120 mg/2 ml powder and solvent for injectable solution is available in packages containing 1 vial with powder + 1 ampoule of solvent (2 ml).
CORTRIUM 500 mg powder for injectable solution is available in packages containing 1 vial.

Marketing Authorization Holder
ESSETI Farmaceutici S.r.l. – Via R. De Cesare, 7 – 80132 Napoli
Responsible Manufacturer for Batch Release
LABORATORIO ITALIANO BIOCHIMICO FARMACEUTICO LISAPHARMA SPA - Via Licinio, 11 -
22036 Erba (Como), Italy

The following information is intended exclusively for physicians and healthcare professionals:
INCOMPATIBILITIES
To avoid compatibility and stability issues, it is recommended to administer methylprednisolone sodium
succinate separately from other substances administered intravenously. Medications that are physically incompatible in solution with methylprednisolone sodium succinato include, but are not limited to: allopurinol sodium, doxapram hydrochloride, tigecycline, diltiazem hydrochloride, as well as calcium gluconate, vecuronium bromide, rocuronium bromide, besylate cisatracurium, glycopyrronium, propofol.

DOSAGE
The dose must be determined based on the clinical condition being treated and its severity.
It is recommended to use the lowest effective dose for the shortest possible duration.
Treatment should be adjusted according to the observed response, and maintenance therapy should be established through gradual titration to achieve an adequate clinical response.
In case of long-term treatment, the drug should be discontinued gradually (see "Warnings and Precautions").
After completion of emergency treatment, consider using a longer-acting injectable formulation or an oral formulation.
In case of high-dose treatment, the recommended dose of CORTRIUM is 30 mg/kg administered intravenously over a period of at least 30 minutes. The dose may be repeated every 4–6 hours within 48 hours. High-dose treatment should be continued until clinical stabilization; however, it should not be prolonged beyond 48–72 hours. Short-term use of high doses may lead to the development of peptic ulcer; therefore, concomitant prophylactic treatment is recommended (see "Warnings and Precautions" and "Undesirable Effects").

Exacerbations of systemic lupus erythematosus and edematous states caused by glomerulonephritis or lupus nephritis:
Pulsed intravenous administration of 250–1000 mg per day for 1–3 days is recommended.
In case of exacerbation of pathological conditions or lack of response to standard therapies, the following intravenous boluses are recommended:

Multiple sclerosis
1 g per day intravenously for 3–5 days

Acute spinal cord injuries
Treatment should be initiated within 8 hours of trauma with a bolus dose of 30 mg/kg administered over 15 minutes, followed by a 45-minute interval and then a maintenance infusion of 5.4 mg/kg/hour for the next 23 hours.
Treatment choice must be individualized, with careful risk/benefit assessment, and in accordance with official guidelines.
Strict monitoring of the patient is also required due to the high risk of toxicity associated with the high dose of methylprednisolone administered.

Palliative therapy in advanced-stage cancer
The recommended dose is 125 mg per day; short-term treatment should be carefully evaluated on a case-by-case basis.

Prevention of nausea and vomiting associated with mildly or moderately emetogenic chemotherapy:
125–250 mg of CORTRIUM, possibly in combination with a phenothiazine, one hour before chemotherapy.
This is followed by a second dose of CORTRIUM at the time of chemotherapy and a final dose before discharge.

Prophylaxis of nausea and vomiting associated with highly emetogenic chemotherapy:
250 mg of CORTRIUM combined with 1–2.5 mg of droperidol or 1.5–2 mg/kg of metoclopramide, one hour before chemotherapy.
This is followed by a second dose of CORTRIUM at the time of chemotherapy and a final dose before discharge.
In all cases, short duration of treatment is recommended.

Adjuvant therapy of severe Pneumocystis jiroveci pneumonia in patients with AIDS
0.5 mg/kg every 6 hours for 10 days.
Administration must begin within 72 hours of starting antimicrobial therapy.

For other indications, the initial dose is 10–40 mg of methylprednisolone, depending on the severity of the clinical condition.
In acute and severe conditions, higher doses may be required. In such cases, short duration of treatment is strongly recommended.
The initial dose should be administered intravenously over several minutes.
Subsequent doses may be given intravenously or intramuscularly; the choice of route should consider the condition being treated and the response achieved.
Corticosteroid therapy is adjuvant and not a substitute for conventional therapy.
If remission occurs during treatment of a chronic disease, the drug should be discontinued (see "Warnings and Precautions").

Paediatric population
In children over 3 years of age, the dose should be determined not by age or weight, but by the severity of the condition and the response obtained.
The daily dose should not be less than 0.5 mg/kg.
Dosage should be gradually reduced if treatment has been prolonged for several days.

METHOD OF ADMINISTRATION
Remove the protective cap from the vial and proceed as usual.
CORTRIUM may be administered by intravenous or intramuscular injection, by intravenous infusion, or via infusion pump.
In emergency situations, the intravenous route is preferred.
For intramuscular and intravenous injections, no further dilution is required. For intravenous infusions, dilute CORTRIUM in a volume of 100 to 1000 ml of 5% glucose solution or physiological saline.
After dilution or reconstitution, CORTRIUM must be used within 4 hours.

UNDESIRABLE EFFECTS
When administered via contraindicated routes (intrathecal/epidural), the following adverse reactions have been reported: arachnoiditis, gastrointestinal/bladder dysfunction, headache, meningitis, paraparesis/paraplegia, seizures, sensory disturbances. The frequency of these adverse reactions is unknown.

For further information, refer to the SmPC (Summary of Product Characteristics).